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α-Lactalbumin is a protein present in the milk of almost all mammalian species.[4] In primates, alpha-lactalbumin expression is upregulated in response to the hormone prolactin and increases the production of lactose.[5]

α-Lactalbumin forms the regulatory subunit of the lactose synthase (LS) heterodimer and β-1,4-galactosyltransferase (beta4Gal-T1) forms the catalytic component. Together, these proteins enable LS to produce lactose by transferring galactose moieties to glucose. As a multimer, alpha-lactalbumin strongly binds calcium and zinc ions and may possess bactericidal or antitumor activity. A folding variant of human alpha-lactalbumin that may form in acidic environments such as the stomach, called HAMLET, probably induces apoptosis in tumor and immature cells.[1] The corresponding folding dynamics of alpha-lactalbumin is thus highly unusual.[6]

The structure of alpha-lactalbumin is well known and is composed of 123 amino acids and 4 disulfide bridges. The molecular weight is 14178 Da, and the isoelectric point is between 4.2 and 4.5. One of the main structural differences with beta-lactoglobulin is that it does not have any free thiol group that can serve as the starting-point for a covalent aggregation reaction. As a result, pure α-lactalbumin will not form gels upon denaturation and acidification.

The sequence comparison of α-lactalbumin shows a strong similarity to that of lysozymes, specifically the Ca2+-binding c-lysozyme.[7] So the expected evolutionary history is that gene duplication of the c-lysozyme was followed by mutation.[4] This gene predates the last common ancestor of mammals and birds, which probably puts its origin at about 300 Ma.[8]